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Identification of enhancer-promoter contacts in squamous cancer cells [RNA-seq]

ABSTRACT: Gene expression profiling in squamous cancer cells under different genetic or chemical perturbations

ORGANISM(S): Homo sapiens

PROVIDER: GSE166233 | GEO | 2021/10/19

REPOSITORIES: GEO

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Identification of enhancer-promoter contacts in squamous cancer cells [HiChIP]

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Identification of enhancer-promoter contacts in squamous cancer cells [ChIP-seq]

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Identification of enhancer-promoter contacts in squamous cancer cells

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Identification of enhancer-promoter contacts in squamous cancer cells [HiChIP]

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Identification of enhancer-promoter contacts in squamous cancer cells

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Identification of enhancer-promoter contacts in squamous cancer cells [RNA-seq]

Project description:Identification of enhancer-promoter contacts in squamous cancer cells [RNA-seq]

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Effects of supercoiling on enhancer-promoter contacts.

Project description:Using Brownian dynamics simulations, we investigate here one of possible roles of supercoiling within topological domains constituting interphase chromosomes of higher eukaryotes. We analysed how supercoiling affects the interaction between enhancers and promoters that are located in the same or in neighbouring topological domains. We show here that enhancer-promoter affinity and supercoiling act synergistically in increasing the fraction of time during which enhancer and promoter stay in contact. This stabilizing effect of supercoiling only acts on enhancers and promoters located in the same topological domain. We propose that the primary role of recently observed supercoiling of topological domains in interphase chromosomes of higher eukaryotes is to assure that enhancers contact almost exclusively their cognate promoters located in the same topological domain and avoid contacts with very similar promoters but located in neighbouring topological domains.

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The first enhancer in an enhancer chain safeguards subsequent enhancer-promoter contacts from a distance.

Project description:BackgroundRobustness and evolutionary stability of gene expression in the human genome are established by an array of redundant enhancers.ResultsUsing Hi-C data in multiple cell lines, we report a comprehensive map of promoters and active enhancers connected by chromatin contacts, spanning 9000 enhancer chains in 4 human cell lines associated with 2600 human genes. We find that the first enhancer in a chain that directly contacts the target promoter is commonly located at a greater genomic distance from the promoter than the second enhancer in a chain, 96 kb vs. 45 kb, respectively. The first enhancer also features higher similarity to the promoter in terms of tissue specificity and higher enrichment of loop factors, suggestive of a stable primary contact with the promoter. In contrast, a chain of enhancers which connects to the target promoter through a neutral DNA segment instead of an enhancer is associated with a significant decrease in target gene expression, suggesting an important role of the first enhancer in initiating transcription using the target promoter and bridging the promoter with other regulatory elements in the locus.ConclusionsThe widespread chained structure of gene enhancers in humans reveals that the primary, critical enhancer is distal, commonly located further away than other enhancers. This first, distal enhancer establishes contacts with multiple regulatory elements and safeguards a complex regulatory program of its target gene.

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Exploring 3D chromatin contacts in gene regulation: The evolution of approaches for the identification of functional enhancer-promoter interaction.

Project description:Mechanisms underlying gene regulation are key to understand how multicellular organisms with various cell types develop from the same genetic blueprint. Dynamic interactions between enhancers and genes are revealed to play central roles in controlling gene transcription, but the determinants to link functional enhancer-promoter pairs remain elusive. A major challenge is the lack of reliable approach to detect and verify functional enhancer-promoter interactions (EPIs). In this review, we summarized the current methods for detecting EPIs and described how developing techniques facilitate the identification of EPI through assessing the merits and drawbacks of these methods. We also reviewed recent state-of-art EPI prediction methods in terms of their rationale, data usage and characterization. Furthermore, we briefly discussed the evolved strategies for validating functional EPIs.

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